Worthylake D K, Wang H, Yoo S, Sundquist W I, Hill C P
Biochemistry Department, University of Utah Medical School, 50 North Medical Drive, Salt Lake City, Utah 84132, USA.
Acta Crystallogr D Biol Crystallogr. 1999 Jan;55(Pt 1):85-92. doi: 10.1107/S0907444998007689. Epub 1999 Jan 1.
The human immunodeficiency virus type I (HIV-1) capsid protein is initially synthesized as the central domain of the Gag polyprotein, and is subsequently proteolytically processed into a discrete 231-amino-acid protein that forms the distinctive conical core of the mature virus. The crystal structures of two proteins that span the C-terminal domain of the capsid are reported here: one encompassing residues 146-231 (CA146-231) and the other extending to include the 14-residue p2 domain of Gag (CA146-p2). The isomorphous CA146-231 and CA146-p2 structures were determined by molecular replacement and have been refined at 2.6 A resolution to R factors of 22.3 and 20.7% (Rfree = 28.1 and 27.5%), respectively. The ordered domains comprise residues 148-219 for CA146-231 and 148-218 for CA146-p2, and their refined structures are essentially identical. The proteins are composed of a 310 helix followed by an extended strand and four alpha-helices. A crystallographic twofold generates a dimer that is stabilized by parallel packing of an alpha-helix 2 across the dimer interface and by packing of the 310 helix into a groove created by alpha-helices 2 and 3 of the partner molecule. CA146-231 and CA146-p2 dimerize with the full affinity of the intact capsid protein, and their structures therefore reveal the essential dimer interface of the HIV-1 capsid.
I型人类免疫缺陷病毒（HIV-1）衣壳蛋白最初作为Gag多聚蛋白的中央结构域合成，随后经蛋白水解加工成一种由231个氨基酸组成的离散蛋白，该蛋白形成成熟病毒独特的锥形核心。本文报道了两种跨越衣壳C末端结构域的蛋白质的晶体结构：一种包含146-231位残基（CA146-231），另一种延伸至包括Gag的14个残基的p2结构域（CA146-p2）。同晶型的CA146-231和CA146-p2结构通过分子置换确定，并分别在2.6 Å分辨率下精修至R因子为22.3%和20.7%（Rfree = 28.1%和27.5%）。对于CA146-231，有序结构域包括148-219位残基，对于CA146-p2，有序结构域包括148-218位残基，它们的精修结构基本相同。这些蛋白质由一个310螺旋、一条延伸链和四个α螺旋组成。一个晶体学二重轴产生一个二聚体，该二聚体通过α螺旋2在二聚体界面的平行堆积以及310螺旋堆积到由伙伴分子的α螺旋2和3形成的凹槽中而稳定。CA146-231和CA146-p2以完整衣壳蛋白的完全亲和力二聚化，因此它们的结构揭示了HIV-1衣壳的基本二聚体界面。
